Rationale: Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. Objectives: To explore the effect of screening with low-dose spiral CT (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage, resectability and survival. Methods: Male subjects, aged 60-75, smokers of 20+ pack-years were randomized to screening with low-dose spiral CT or control. All participants underwent a baseline, once-only chest X-ray (CXR) and sputum cytology examination. Screening-arm subjects had LDCT upon accrual, to be repeated every year for four additional years, while controls had a yearly medical examination only. Measurements and Main Results: 2472 cases (LDCT 1276, control 1196) were randomized. After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) LDCT patients and 34 (2.8%) controls (p=0.016). Stage I rates were 54% and 34% respectively (p=0.06), and complete resectability rates were 60% and 50% (p=0.35). Five-year actuarial survival of lung cancer patients was slightly better (p=0.08), and less symptomatic cases were detected in the screening arm. However, the number of advanced lung cancer cases was the same. 20 LDCT patients (1.6%) and 20 controls (1.7%) have died of lung cancer, while 26 and 25 respectively have died of other causes. Conclusions: A small stage-shift in favor of the screening arm was observed, while resection rates, advanced case rates and disease-specific mortality were similar. Lung cancer screening by spiral CT should not be advertised or proposed outside research programs.

Clinical Trials Registry information: I.D. #NCT00420862, available at www.clinicaltrials.gov